The Royal Australasian College of Surgeons

purpose

This guideline includes statements and recommendations based on available, high level evidence about the use of endocrine therapy for pre-menopausal and post-menopausal women with hormone receptor-positive advanced breast cancer. The guideline aims to provide health professionals with information to assist in making management recommendations for improved patient outcomes. National Breast and Ovarian Cancer Centre (NBOCC) also develops information specifically for consumers about advanced breast cancer diagnosis and treatment options.

For information on the Pharmaceutical Benefits Scheme (PBS) listing for drugs mentioned in the guideline please see page 19 of this guideline.

recommendations for use of

Endocrine therapyfor the treatment of hormone receptor-positive advanced breast cancer

JUNE 2008 | Incorporates published evidence to July 2007

Endorsed by:

A CLINICAL PRACTICE GUIDELINE DEVELOPED BY NATIONAL BREAST AND OVARIAN CANCER CENTRE (NBOCC)

This document supplements guideline recommendations 22, 24a and 24b about the use of endocrine therapy in National Breast Cancer Centre* Clinical practice guidelines for the management of advanced breast cancer, 2nd edition, 2001 (page 9).1

BacKGround

Endocrine therapy is a type of treatment, that acts to inhibit the growth of breast cancer cells which have hormone receptors. It does this by blocking either the production of female hormones or the ability of hormones to interact with receptors on cancer cells.

Endocrine therapies include:

• ovarian suppression/ablation, e.g. luteinising hormone-releasing hormone agonists (goserelin, buserelin), ovarian irradiation, and surgical oophorectomy

• selective oestrogen receptor modulators, e.g. tamoxifen

• selective oestrogen receptor downregulators, e.g. fulvestrant

• progestins, e.g. megestrol acetate and medroxyprogesterone

• aromatase inhibitors, e.g. anastro�ole, exemestane, letro�ole.tors, e.g. anastro�ole, exemestane, letro�ole.

This guideline is based on a meta-analysis2 and an evidence review.3 The meta-analysis is about the use of endocrine therapy in pre-menopausal women with hormone receptor-positive advanced breast cancer. The evidence review is about the use of endocrine therapy in post-menopausal women with hormone receptor-positive advanced breast cancer. The evidence is not specific to women with metastatic (stage IV) breast cancer. While the majority of women had stage IV metastatic disease, a small number of women with locally advanced disease and/or locoregional recurrence were included in the trials. In the majority of trials, women with tumours of unknown hormone receptor status were also eligible for participation.

A previous Cochrane review (2003)4 investigating randomised trials comparing the effects of chemotherapy alone with endocrine therapy alone in women with metastatic breast cancer found that endocrine therapy is the preferred first-line treatment for women with hormone receptor-positive breast cancer, except in the presence of rapidly progressive disease. The review also found that the incidence of adverse events is less frequent with endocrine therapy compared with chemotherapy.

summarY of eVidence

Use of endocrine therapy for pre-menopausal women with hormone receptor-positive advanced breast cancer

The statements and recommendations about pre-menopausal women are based on evidence from a meta-analysis2 of four randomised trials. The trials compared the use of luteinising hormone-releasing hormone (LH-RH) agonist alone compared with the use of LH-RH agonist plus tamoxifen in pre-menopausal women with advanced breast cancer.

Combined therapy of LH-RH agonist plus tamoxifen significantly improved overall survival and progression-free survival compared with LH-RH agonist alone in pre-menopausal women with advanced breast cancer. Another trial5 found a significant improvement in survival outcomes for women treated with combined LH-RH agonist plus tamoxifen compared with tamoxifen alone. This trial also found a significantly reduced incidence of hot flushes in women treated with tamoxifen alone.

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All trials investigating the use of endocrine therapy in pre-menopausal women used a LH-RH agonist. Although not formally compared in a trial setting, it is reasonable to assume that all forms of ovarian ablation or ovarian functional suppression are equivalent and have similar effects.

Use of endocrine therapy for post-menopausal women with hormone receptor-positive advanced breast cancer

The statements and recommendations about post-menopausal women are based on evidence from 14 randomised trials assessing the use of endocrine therapy for post-menopausal women with hormone receptor-positive advanced breast cancer:

• five trials compared a third generation aromatase inhibitor with tamoxifen as first-line therapy6-10

• five trials compared a third generation aromatase inhibitor with progestins (megestrol acetate) as second-line therapy11-15

• two trials compared a third generation aromatase inhibitor with fulvestrant as second-line therapy16,17

• two trials compared one third generation aromatase inhibitors with another.18,19 (see table 1 on page 11 for trial details)

As first-line therapy, aromatase inhibitors significantly improved progression-free survival and overall response rate compared with tamoxifen in post-menopausal women with hormone receptor-positive advanced breast cancer. Improvements in overall survival have not been demonstrated. Overall, there was no significant difference in total adverse events between aromatase inhibitors and tamoxifen, although the incidence of vaginal bleeding and thromboembolic events was significantly lower in women treated with aromatase inhibitors. One study reported that quality of life was comparable for aromatase inhibitors and tamoxifen.3

As second-line therapy, aromatase inhibitors significantly improved progression-free survival and overall survival for women compared with progestins. Overall, both treatments were well tolerated. Patients treated with aromatase inhibitors experienced significantly higher incidence of nausea, hot flushes, and diarrhoea but a significantly lower incidence of dyspnoea compared with patients treated with progestins. Where reported, quality of life data comparing aromatase inhibitors and progestins are conflicting and no firm conclusions can be drawn. There were no significant differences in efficacy or safety with the use of aromatase inhibitors compared with fulvestrant.3

Of the two trials that compared one aromatase inhibitor with another, treatment was administered first-line in one trial18 and second-line in the other.19 Superiority of one aromatase inhibitor over another is yet to be determined.

* In February 2008, National Breast Cancer Centre incorporating the Ovarian Cancer Program (NBCC) changed its name to National Breast and Ovarian Cancer Centre (NBOCC)

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statements and recommendations

statements LeVeL of eVidence20

reference

in women with hormone receptor-positive advanced breast cancer:

Endocrine therapy is preferred for women with hormone receptor-positive advanced breast cancer in preference to chemotherapy except in the presence of rapidly progressive visceral disease

I Cochrane 20034

Endocrine therapy shows no significant difference in overall survival compared with chemotherapy

I Cochrane 20034

Incidence of adverse events including nausea, vomiting and alopecia is less frequent with endocrine therapy compared with chemotherapy

I Cochrane 20034

in pre-menopausal women with hormone receptor-positive advanced breast cancer:

Combination of luteinising hormone-releasing hormone (LH-RH) agonist and tamoxifen shows significant benefit in overall survival, progression-free survival and overall response rate compared with LH-RH agonist alone

I Klijn 20012

Combination of LH-RH agonist and tamoxifen shows significant benefit in overall survival, progression-free survival and overall response rate compared with tamoxifen alone

III Klijn 20005

Incidence of hot flushes is significantly higher in women treated with combined tamoxifen and LH-RH agonist compared with tamoxifen alone

III Klijn 20005

There are insufficient data to guide the use of third generation aromatase inhibitors in combination with functional ovarian ablation/suppression or fulvestrant in pre-menopausal women

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statements LeVeL of eVidence

reference

in post-menopausal women with hormone receptor-postive advanced breast cancer:

Combination of aromatase inhibitors and trastu�umab in women with HER2-positive hormone dependent advanced breast cancer leads to improved progression-free survival compared with aromatase inhibitors alone

II NBCC21

First-line therapy

Third generation aromatase inhibitorsa show no significant difference in overall survival compared with tamoxifen

I NBOCC3

Third generation aromatase inhibitorsb show significant benefit in progression-free survival compared with tamoxifen

I NBOCC3

Third generation aromatase inhibitorsc show significant benefit in overall response rate compared with tamoxifen

I NBOCC3

Adverse events

Overall incidence of adverse events is not significantly different between third generation aromatase inhibitors and tamoxifen

I NBOCC3

Incidence of thromboembolic events and vaginal bleeding is significantly lower with third generation aromatase inhibitors compared with tamoxifen

I NBOCC3

Incidence of arthralgia, diarrhoea, dyspnoea, hot flushes, and nausea is not significantly different with third generation aromatase inhibitors compared with tamoxifen

I NBOCC3

Quality of life

There are insufficient data to indicate any differences in quality of life between third generation aromatase inhibitors and tamoxifen

a Trials relate to anastro�oleb Trials relate to anastro�ole, letro�ole

c Trials relate to anastro�ole, exemestane, letro�ole

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statements LeVeL of eVidence

reference

second-line therapy(following progression on tamoxifen)

Third generation aromatase inhibitorsc show significant benefit in overall survival and progression-free survival compared with progestinsd

I NBOCC3

Third generation aromatase inhibitorsc show no significant difference in overall response rate compared with progestins

I NBOCC3

Third generation aromatase inhibitors show no significant difference in overall survival compared with fulvestranta

II NBOCC3

Third generation aromatase inhibitors show no significant difference in progression-free survival and overall response rate compared with fulvestrante

I NBOCC3

Adverse events

Overall incidence of adverse events is not significantly different with third generation aromatase inhibitors compared with progestins

I NBOCC3

Incidence of dyspnoea is significantly lower with third generation aromatase inhibitors compared with progestins

I NBOCC3

Incidence of nausea, hot flushes and diarrhoea is significantly higher with third generation aromatase inhibitors compared with progestins

I NBOCC3

There are no significant differences in the incidence of thromboembolic events, vaginal bleeding and arthralgia between third generation aromatase inhibitors and progestins

I NBOCC3

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statements LeVeL of eVidence

reference

Quality of life

Where reported there is conflicting evidence about quality of life and no firm conclusions can be drawn

II NBOCC3

Aromatase inhibitor vs aromatase inhibitor

There are insufficient data to indicate a significant difference in overall survival, progression free survival or overall response rate for one aromatase inhibitor over another aromatase inhibitorf

a Trials relate to anastro�olec Trials relate to anastro�ole, exemestane, letro�ole d Trials relate to megastrol acetatee Trials relate to anastro�ole and exemestanef For trial details please see table 1 on page 11

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recommendations LeVeL of eVidence20

reference

in women with hormone receptor-positive advanced breast cancer:

Endocrine therapy is recommended in preference to chemotherapy except in the presence of rapidly progressive visceral disease

I Cochrane 20034

Information about the treatment should be discussed with the patient. The patient should be adequately prepared for the treatment

I NBCC & NCCI22

in pre-menopausal women with hormone receptor-positive advanced breast cancer:

Tamoxifen combined with luteinising hormone-releasing hormone (LH-RH) agonist is recommended in favour of a LH-RH agonist alone

I Klijn 20012

If commencing treatment with tamoxifen alone, consideration should be given to adding a LH-RH agonist, if response is not optimal

III Klijn 20005

Optimal dose and schedule of administration

Recommended doses and schedule are:Tamoxifen 20mg/dayGoserelin 3.6mg subcutaneously monthly

Therapeutic Goods

Administration23

Recommendations to individuals should be based on the risks, the absolute benefits and harms of treatment, and their personal preference. These factors should be discussed with the woman. Women receiving endocrine therapy should be reviewed regularly and monitored for adverse events by clinicians familiar with endocrine therapy.

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recommendations LeVeL of eVidence

reference

in post-menopausal women with hormone receptor-positive advanced breast cancer:

Aromatase inhibitors with trastu�umab are recommended for the treatment of women with HER2-positive hormone dependent advanced breast cancer in preference to aromatase inhibitors alone

II NBCC21

First-line treatment

Third generation aromatase inhibitors are recommended in preference to tamoxifen

I NBOCC3

Second-line treatment(following progression on tamoxifen)

Third generation aromatase inhibitors are recommended in preference to progestins

I NBOCC3

Optimal dose, schedule and duration of administration

Continued use of third generation aromatase inhibitors is recommended until disease progression or unacceptable toxicity

I NBOCC3

Recommended doses and schedules for third generation aromatase inhibitors are:Anastro�ole 1.0 mg/dayExemestane 25 mg/dayLetro�ole 2.5 mg/day

I NBOCC3

There are insufficient data to recommend one type of endocrine therapy over another for women who have progressed during or after treatment with adjuvant aromatase inhibitors

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summarY of triaL resuLts

endocrine tHerapY in pre-menopausaL Women

A meta-analysis of four trials2 found that there was a significant overall survival benefit (p=0.02) and progression-free survival benefit (p=0.0003) for pre-menopausal women treated with combined tamoxifen and LH-RH agonist compared to pre-menopausal women treated with LH-RH agonist alone. One trial5 found that the incidence of hot flushes was significantly higher in women treated with combined tamoxifen and LH-RH agonist compared with women treated with tamoxifen alone (87% vs 40%; p=0.0001). There are currently insufficient data to guide the use of third generation aromatase inhibitors in combination with functional ovarian ablation/suppression or fulvestrant in pre-menopausal women. Further research is required to investigate the use of third generation aromatase inhibitors and fulvestrant in the pre-menopausal setting.

Overall survival

First-line therapy

A meta-analysis of two trials6,7 revealed third generation aromatase inhibitors confer no survival advantage over tamoxifen as first-line therapy for advanced breast cancer (p=0.98).

Second-line therapy

As second-line therapy a meta-analysis of four trials11-13,15 showed significant improvement in overall survival for women treated with third generation aromatase inhibitors compared with progestins (p=0.003). One trial showed a median survival benefit of 4.2 months.11

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endocrine tHerapY in post-menopausaL Women

Table 1: Details of trials of endocrine therapy for post-menopausal women�

triaL interVention comparator position in treatment sequence

Aromatase inhibitor vs antioestrogen

Bonneterre 2001 Anastro�ole 1.0 mg/day Tamoxifen 20 mg/day First-line for advanced disease

Milla-Santos 2003 Anastro�ole 1.0 mg/day Tamoxifen 40 mg/day First-line for advanced disease

Paridaens 2003/4 Exemestane 25 mg/day Tamoxifen 20 mg/day First-line hormonal therapy for metastatic disease (≤1 CT regimen permitted)

Mouridsen 2001 Letro�ole 2.5 mg/day Tamoxifen 20 mg/day First-line hormonal therapy for metastatic disease (≤1 CT regimen permitted)

Batra 2006 Letro�ole 2.5 mg/day Tamoxifen 20 mg/day First-line for metastatic or recurrent disease

Mauriac 2003 Anastro�ole 1.0 mg/day Fulvestrant 250 mg/month IM

Second-line after endocrine therapy

Gradishar 2006 Exemestane 25 mg/day Fulvestrant IM loading dose regimen a

Second-line after NSAI therapy

aromatase inhibitor vs progestin

Bu�dar 1996 [North American and European trials]

Anastro�ole 1.0 mg/day Megestrol acetate 160 mg/day

Second-line after antioestrogen

Kaufmann 2000 [Trial EXE 018]

Exemestane 25 mg/day Megestrol acetate 160 mg/day

Second-line after antioestrogen

Bu�dar 2001 Letro�ole 2.5 mg/day Megestrol acetate 160 mg/day

Second-line after antioestrogen

Schmid 2001 Letro�ole 2.5 mg/day Megestrol acetate 160 mg/day

Possibly second-line b

Dombernowsky 1998 Letro�ole 2.5 mg/day Megestrol acetate 160 mg/day

Second-line after antioestrogen

aromatase inhibitor vs aromatase inhibitor

Mayordomo 2006 [GEICAM 2001-03]

Anastro�ole 1.0 mg/day Exemestane 25 mg/day First-line hormonal for metastatic disease (previous CT permitted)

Rose 2003 Anastro�ole 1.0 mg/day Letro�ole 2.5 mg/day Second-line after antioestrogen

Notes: CT = chemotherapy; IM = intramuscular; NSAI = nonsteroidal aromatase inhibitora 500 mg on Day 0, 250 mg on Days 14 and 28, and 250 mg every 28 days thereafterb Not explicitly stated in the publication

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Progression-free survival

First-line therapy

A meta-analysis of two trials6,9 revealed that women treated with third generation aromatase inhibitors show significant advantage in progression-free survival (p=0.0001) compared with women treated with tamoxifen (Bonneterre 2001:6 8.5 vs 7 months, Mouridsen 2001:9 9.4 vs 6 months).

Second-line therapy

A meta-analysis of four trials11-13,15 revealed a significant benefit in progression-free survival for women treated with third generation aromatase inhibitors compared to progestins (p=0.01). A meta-analysis of two trials16,17 revealed no significant difference in progression-free survival between women treated with a third generation aromatase inhibitor compared with women treated with fulvestrant (p=0.31).

Overall response rate

First-line therapy

As first-line therapy a meta-analysis of four trials6-9 showed that third generation aromatase inhibitors are statistically superior to tamoxifen with respect to tumour response (p=0.004).

Second-line therapy

All five trials11-15 in the meta-analysis found that overall response rate was higher in women treated with third generation aromatase inhibitors compared with women treated with progestins, although this difference was not significant. No trial has shown a statistically significant difference in overall response rate between women treated with third generation aromatase inhibitors compared with women treated with fulvestrant.

Comparing the efficacy of aromatase inhibitors

As first-line therapy, anastro�ole and exemestane were not significantly different with respect to overall survival, progression-free survival, or overall response rate.

As second-line therapy, anastro�ole and letro�ole were equivalent in terms of overall survival and progression-free survival. Letro�ole was statistically more effective than anastro�ole in terms of overall response rate (19% vs 12%; p=0.014).19 This was not the case when women whose receptor status was unknown were excluded from the analysis.

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Adverse events

First-line therapy

A meta-analysis6,7,9 of three trials showed no significant difference overall in adverse events between women treated with aromatase inhibitors compared with tamoxifen (p=0.25).

The largest trial in this meta-analysis (Bonneterre)6 reported an overall incidence of adverse events with aromatase inhibitors of 83% compared with 85% for tamoxifen. However the incidence of vaginal bleeding was significantly lower in women treated with a third generation aromatase inhibitor compared with tamoxifen (p<0.001), as was the incidence of thromboembolic events (p=0.003).

Second-line therapy

There was no significant difference16,17 in overall incidence of adverse events between women treated with third generation aromatase inhibitors compared with women treated with fulvestrant (89% vs 89%; p=0.79). The incidence of specific adverse events (nausea, diarrhoea, rash, arthralgia, hot flashes, thromboembolic events and dyspnoea) was similar for both groups. The incidence of vaginal bleeding was not reported.

A meta-analysis of three trials12,13,15 showed no significant difference overall in adverse events for women treated with third generation aromatase inhibitors compared with progestins (p=0.31). There was however a significant increase of nausea (p=0.005), hot flushes (p<0.001), and diarrhoea (p<0.001) in women treated with a third generation aromatase inhibitor compared with women treated with a progestin. In contrast, the incidence of dyspnoea was significantly lower in women treated with aromatase inhibitors compared with progestins (p<0.0001).

Quality of life

Quality of life was poorly assessed and poorly reported across the trials and therefore no firm conclusions can be drawn. Most studies that did report on quality of life found that there was no significant difference between endocrine therapies. Further research is required to determine the short-and long-term effects of endocrine therapy on quality of life.

strenGtHs and WeaKness of eVidence

Only four trials7,10,17,18 investigating the use of endocrine therapy in post-menopausal women specifically recruited patients with hormone receptor-positive disease. Hormone receptor status of participants was not explicitly stated in the Schmid (2001)14 publication. In all other trials, patients with unknown hormone receptor status were eligible to participate in the trials. Across all studies there was no consistent definition of ‘advanced breast cancer’.

The overall survival data from the included studies should be interpreted with caution due to the uncontrolled nature of treatment post-progression. In two post-menopausal trials patients crossed over to the alternate therapy on disease progression. In other trials, treatment following disease progression and study drug discontinuation was at the discretion of the investigator. Post-progression therapies may therefore have impacted on overall survival. Information about long-term results on overall survival and adverse events is not yet available.

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Clinical practice recommendations developed by NBOCC will be reviewed and revised as required as additional significant evidence becomes available.

unansWered questions

Important unanswered questions about the use of endocrine therapy in hormone receptor-positive advanced breast cancer are outlined below; some of these may be addressed in ongoing trials:

• the use of third generation aromatase inhibitors and fulvestrant in pre-menopausal women

• which endocrine therapy is recommended for women who have progressed on adjuvant aromatase inhibitors

• the relative benefits and harms of different aromatase inhibitors

• the relative benefits and harms of fulvestrant

• quality-of-life issues associated with endocrine therapy

• long-term side effects associated with the use of endocrine therapy.

onGoinG and additionaL triaLs

A number of ongoing randomised trials are investigating the use of endocrine therapy in hormone receptor-positive advanced breast cancer:

• four ongoing trials investigating the use of endocrine therapy in pre-menopausal women with advanced breast cancer (D8664C00008, Zoladex ABC Study;24 FHCRC-6412, UWCC-UW 6412;25 SWOG-8692;26 MSHMC-1609)

• three ongoing trials investigating the use of endocrine therapy as first-line therapy for advanced breast cancer (FIRST;27 SWOG-S0226;28 EORTC-1095129)

• three ongoing trials investigating the use of endocrine therapy as second-line therapy for advanced breast cancer (ICR-CTSU Sofea;30 D6997L00004;31 EFECT32)

• two ongoing trials comparing one aromatase inhibitor with another in advanced breast cancer (A5991048;33 GEICAM 2001-03.34)

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references1 National Breast Cancer Centre. Clinical practice guidelines for the management of advanced breast

cancer. Canberra: Commonwealth of Australia 2001.

2 Klijn JGM, Blamey RW, Boccardo F, et al. Combined tamoxifen and luteini�ing hormone-releasing hormone (LH-RH) agonist versus LH-RH agonist alone in premenopausal advanced breast cancer: A meta-analysis of four randomi�ed trials. J Clin Oncol 2001;19(2):343–353.

3 National Breast and Ovarian Cancer Centre. Evidence of the use of endocrine therapy for post-menopausal women with metastatic breast cancer. National Breast and Ovarian Cancer Centre, Surry Hills, NSW, 2008.

4 Wilcken N, Hornbuckle J, Ghersi D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer. Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD002747. DOI: 10.1002/14651858.CD002747.

5 Klijn JGM, Beex VAM, Mauriac L, et al. Combined Treatment With Buserelin and Tamoxifen in Premenopasual Metastatic Breast Cancer: A Randomised Study. J Nat Cancer Inst 2000; 92 (11): 903–911.

6 Bonneterre J, Bu�dar A, Nabholt� JA, et al. Anastro�ole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001;92(9):2247–58.

7 Milla-Santos A, Milla L, Portella J, et al. Anastro�ole versus tamoxifen as first-line therapy in postmenopausal patients with hormone-dependent advanced breast cancer. A J Clin Oncol 2003; 26(3):317–22.

8 Paridaens R, Dirix L, Lohrisch C, et al. Mature results of a randomi�ed phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. Ann Oncol 2003;14:1391–8.

9 Mouridsen H, Gershanovich M, Sun Y, et al. Superior efficacy of letro�ole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the international letro�ole breast cancer group. J Clin Oncol 2001;19(10):2596–606.

10 Batra U, Jacob LA, Saini KS, Dadhich HK. To analy�e the efficacy, tolerability and pharmaco economics of letro�ole vs. tamoxifen as first-line therapy in post menopausal, hormone positive females with metastatic or recurrent breast cancer. Ann Oncol 2006;17(Suppl 9): ix77.

11 Bud�ar A, Jonat W, Howell A, et al. Anastro�ole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analsyis of two phase III trials. J Clin Oncol 1996;14(2000–11).

12 Kaufmann M, Bajetta E, Dirix LY, et al. Exemestane improves survival compared with megestrol acetate in postmenopausal patients with advanced breast cancer who have failed on tamoxifen: results of a double-blind randomised phase III trial. Euro Cancer 2000;36(Suppl):81–91.

13 Bu�dar A, Douma J, Davidson N, et al. Phase III, multicenter, double-blind, randomi�ed study of letro�ole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol 2001;19(14):3357–66.

14 Schmid P, Wischnewsky MB, Possinger K. Self organi�ing maps and prognosis of advanced breast cancer patients with bone metastases receiving letro�ole or MA. Breast Cancer Res and Treat 2001;64:77.

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15 Dombernowsky P, Smith I, Falkson G, et al. Letro�ole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomi�ed trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol 1998;16(2):453–61.

16 Mauriac L, Pippen JE, Quaresma Albano J, Gertler SZ, Osborne CK. Fulvestrant (Faslodex) versus anastro�ole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. Euro J Cancer 2003;39(9):1228–33.

17 Gradishar W, Chia S, Piccart M, on behalf of the EFECT writing committee. Fulvestrant versus exemestane following prior non-steroidal aromatase inhibitor therapy: first results from EFECT, a randomi�ed, phase III trial in postmenopausal women with advanced breast cancer. 29th Annual San Antonio Breast Cancer Symposium, December 2006, Abstract 12.

18 Mayordomo J, Llombart A, Martin M, et al. Randomi�ed, multicenter, crossover phase II trial to compare exemestane (E) vs. anastro�ole (A) in postmenopausal patients (pt) with advanced breast cancer (ABC) and positive hormone receptors (HR). Final efficacy analysis of GEICAM 2001-03 study. ASCO Annual Meeting 2006, abstract no. 638.

19 Rose C, Vtoraya O, Plu�anska A, et al. An open randomised trial of second-line endocrine therapy in advanced breast cancer. Euro J Cancer 2003;39(16):2318–27.

20 National Health and Medical Research Council. How to use the evidence: assessment and application of scientific evidence. Canberra, Commonwealth of Australia, 2000.

21 National Breast Cancer Centre. Recommendations for use of Trastu�umab (Herceptin®) for treatment of HER2-positive breast cancer. NBCC, Camperdown, NSW, 2007.

22 National Breast Cancer Centre and National Cancer Control Initiative. Clinical practice guidelines for the psychosocial care of adults with cancer. NBCC, Camperdown, NSW, 2003.2003.

23 Therapeutic Good Administration http:/www.tga.gov.au/ Accessed October 10, 2007.

24 National Cancer Institute Clinical Trials (PDQ®) D8664C00008, Zoladex ABC Study http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=484695&version=patient&protocolsearchpr=3592790 Accessed August 31, 2007.

25 National Cancer Institute Clinical Trials (PDQ®) UWCC-UW 6412 http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=553612&version=patient&protocolsearchid=3592790 Accessed August 31, 2007.

26 National Cancer Institute Clinical Trials (PDQ®) SWOG-8692 http://www.nci.nih.gov/clinicaltrials/view_clinicaltrials.aspx?version=healthprofessional&cdrid=74317&protocolsearchid=842037 Accessed August 31, 2007.

27 National Cancer Institute Clinical Trials (PDQ®) FIRST http://clinicaltrials.gov/ct/show/NCT00274469?order=1 Accessed August 31, 2007.

28 National Cancer Institute Clinical Trials (PDQ®) SWOG-S0226 http://www.cancer.gov/clinicaltrials/SWOG-S0226 Accessed August 31, 2007.

29 National Cancer Institute Clinical Trials (PDQ®) EORTC-10951 http://www.cancer.gov/clinicaltrials/EORTC-10951 Accessed August 31, 2007.

30 National Cancer Institute Clinical Trials (PDQ®) ICR-CTSU Sofea http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=448616&version=patient&protocolsearchid=3592790 Accessed August 31, 2007.

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31 National Cancer Institute Clinical Trials (PDQ®) D6997L00004 http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=487687&version=HealthProfessional&protocolsearchid=3594517 Accessed August 31, 2007.

32 Clinical Trials EFECT http://clinicaltrials.gov/ct/show/NCT00065325?order=1 Accessed August 31, 2007.

33 National Cancer Institute Clinical Trials (PDQ®) A5991048 http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=447079&version=patient&protocolsearchid=3592790 Accessed August 31, 2007.

34 GEICAM 2001-03 http://www.geicam.org/ingles/protocolgeicam2001-03.htm Accessed August 31, 2007.

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membership of nBocc endocrine therapy subgroup

This guideline was developed by a multidisciplinary working group convened by NBOCC:

Dr Catherine Shannon Medical Oncologist (Chair)

Ms Denice Bassanelli Consumer Representative

Dr Richard De Boer Medical Oncologist

Dr Nicole McCarthy Medical Oncologist

Ms Janet Rice Nurse

Professor Patsy Yates Nurse

membership of nBocc advanced Breast cancer Guidelines Working Group

The development of this guideline was overseen by a multidisciplinary working group convened by NBOCC: Dr Karen Luxford (Facilitator), Dr David Blakey, Professor Phyllis Butow, Ms Helen Collyner, Ms Sally Crossing, Associate Professor Jane Dahlstrom, Dr Craig Murphy, Ms Janet Rice, Dr Catherine Shannon, Ms Ann Town, Professor Patsy Yates

nBocc staff

Ms Ornella Care Senior Project Officer (Project lead)

Dr Karen Luxford General Manager

Ms Alison Pearce Program Manager

systematic review

NBOCC gratefully acknowledges the work of Dr Su�anne Campbell at Health Technology Analyst Pty Ltd in developing the systematic review Evidence on the use of endocrine therapy for post-menopausal women with metastatic breast cancer (2008), which informed the development of this guideline

external review

NBOCC acknowledges those who gave their time to provide comment on the draft guideline recommendations as part of the external review process

acknowledgement

The National Breast Cancer Foundation provided funding for the development and production of this guideline

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pharmaceutical Benefits scheme indications for drugs mentioned in this guideline (as of 1 march 2008). for updates after this date go to http://www.pbs.gov.au

Anastro�ole: Treatment of hormone-dependent breast cancer in post-menopausal women

Exemestane: Treatment of hormone-dependent advanced breast cancer in post-menopausal women with disease progression following treatment with tamoxifen citrate

Letro�ole: Treatment of hormone-dependent advanced breast cancer in post-menopausal women

Goserelin: Hormone-dependent locally advanced (equivalent to stage III) or metastatic (equivalent to stage IV) breast cancer in pre-menopausal women

Megestrol acetate: Treatment of hormone-dependent advanced breast cancer

Tamoxifen: Treatment of hormone-dependent breast cancer. This drug is not subsided for the primary prevention of breast cancer

isBn print: 978-1-74127-089-1 online: 978-1-74127-094-5 cip: 11545

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National Breast and Ovarian Cancer Centre is funded by the Australian Government Department of Health and Ageing.

Full details of trial results are provided in the document Evidence on the use of endocrine therapy for post-menopausal women with metastatic breast cancer (2008), which can be accessed via the NBOCC website at www.nbocc.org.au

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www.nbocc.org.au© National Breast and Ovarian Cancer Centre 2008

Funded by the Australian Government Department of Health and Ageing

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